Pharmacological effects of hydroxychloroquine in patients with COVID-19: Systematic literature review

Authors

DOI:

https://doi.org/10.33448/rsd-v10i8.17193

Keywords:

Hydroxychloroquine; COVID-19; Coronavirus; Treatment.

Abstract

An outbreak of the new coronavirus (COVID-19) started in December 2019, and spread throughout China, spreading to the world in a short time, which requires immediate searches for its treatment. Thus, the use of chloroquine (CQ) and hydroxychloroquine (HCQ) has aroused interest in COVID-19. This systematic review follows the reporting items indicated for systematic reviews and Meta-Analysis Guidelines (PRISMA). The descriptors were selected: “SARS-CoV-2”, “COVID-19”, “Hydroxychloroquine” and “Chloroquine” and included in the databases Science Direct, United States National Library of Medicine (PubMed), Latin American bibliographic information on health sciences (LILACS), Scientific Electronic Library Online (SciELO) and Web of Science to search for studies. After screening, a total of 6.339 studies were found. After reading and applying the eligibility criteria, a total of 8 articles were selected to prepare the outcomes of this review. The results of the studies showed that the use of HCQ has outcomes with no significant improvement in the clinical picture, including association with adverse events (including serious) in patients with COVID-19. Thus, randomized clinical trials did not provide evidence of the efficacy of HCQ in patients with COVID-19, showing that an HCQ is not significantly effective, and has negative results regarding its safety for patients with COVID-19.

References

Barbosa, J., Kaitis, D., Freedman, R., Le, K., & Lin, X. (2020). Clinical outcomes of hydroxychloroquine in hospitalized patients with COVID-19: a quasi-randomized comparative study. N Engl J Med, 1, 8882.

Borba, M., de Almeida Val, F., Sampaio, V. S., Alexandre, M. A., Melo, G. C., Brito, M., & Lacerda, M. (2020). Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study). MedRxiv.

Bosseboeuf, E., Aubry, M., Nhan, T., De Pina, J. J., Rolain, J. M., Raoult, D., & Musso, D. (2018). Azithromycin inhibits the replication of Zika virus. J Antivir Antiretrovir, 10(1), 6-11.

Boulware, D. R., Pullen, M. F., Bangdiwala, A. S., Pastick, K. A., Lofgren, S. M., Okafor, E. C., & Hullsiek, K. H. (2020). A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19. New England Journal of Medicine, 383(6), 517-525.

Campbell, M., McKenzie, J. E., Sowden, A., Katikireddi, S. V., Brennan, S. E., Ellis, S., HartmannBoyce, J., Ryan, R., Shepperd, S., Thomas, J., et al. (2020). Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ 368, l6890.

Channappanavar, R., & Perlman, S. (2017). Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. In Seminars in immunopathology (39, 529-539). Springer Berlin Heidelberg.

Chen, J., Liu, D., Liu, L., Liu, P., Xu, Q., Xia, L., & Lu, H. (2020). A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). Journal of Zhejiang University (Medical Science), 49(1), 0-0.

Colson, P., Rolain, J. M., Lagier, J. C., Brouqui, P., & Raoult, D. (2020). Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents, 55(4), 105932.

Cui, J., Li, F., & Shi, Z. L. (2019). Origin and evolution of pathogenic coronaviruses. Nature Reviews Microbiology, 17(3), 181-192.

Donnelly, C. A., Ghani, A. C., Leung, G. M., Hedley, A. J., Fraser, C., Riley, S., & Anderson, R. M. (2003). Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. The Lancet, 361(9371), 1761-1766.

Fantini, J., Di Scala, C., Chahinian, H., & Yahi, N. (2020). Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. International journal of antimicrobial agents, 55(5), 105960.

Fiolet, T., Guihur, A., Rebeaud, M. E., Mulot, M., Peiffer-Smadja, N., & Mahamat-Saleh, Y. (2021). Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis. Clinical microbiology and infection, 27(1), 19-27.

Forni, D., Cagliani, R., Clerici, M., & Sironi, M. (2017). Molecular evolution of human coronavirus genomes. Trends in microbiology, 25(1), 35-48.

Fteiha, B., Karameh, H., Kurd, R., Ziff‐Werman, B., Feldman, I., Bnaya, A., & Ben‐Chetrit, E. (2020). QTc prolongation among hydroxychloroquine sulfate‐treated COVID‐19 patients: An observational study. International Journal of Clinical Practice, e13767.

Gabriels, J., Saleh, M., Chang, D., & Epstein, L. M. (2020). Inpatient use of mobile continuous telemetry for COVID-19 patients treated with hydroxychloroquine and azithromycin. HeartRhythm Case Reports, 6(5), 241-243.

Gautret, P., Lagier, J. C., Parola, P., Meddeb, L., Mailhe, M., Doudier, B., & Raoult, D. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International journal of antimicrobial agents, 56(1), 105949.

Goel, P., & Gerriets, V. (2019). Chloroquine.

Gu, J., Gong, E., Zhang, B., Zheng, J., Gao, Z., Zhong, Y., & Leong, A. S. Y. (2005). Multiple organ infection and the pathogenesis of SARS. Journal of Experimental Medicine, 202(3), 415-424.

Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., & Pöhlmann, S. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 181(2), 271-280.

Hu, T. Y., Frieman, M., & Wolfram, J. (2020). Insights from nanomedicine into chloroquine efficacy against COVID-19. Nature nanotechnology, 15(4), 247-249.

Huang, M., Tang, T., Pang, P., Li, M., Ma, R., Lu, J., & Shan, H. (2020). Treating COVID-19 with chloroquine. Journal of molecular cell biology, 12(4), 322-325.

Hui, D. S., Azhar, E. I., Madani, T. A., Ntoumi, F., Kock, R., Dar, O., & Petersen, E. (2020). The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health—The latest 2019 novel coronavirus outbreak in Wuhan, China. International journal of infectious diseases, 91, 264-266.

Ip, A., Ahn, J., Zhou, Y., Goy, A. H., Hansen, E., Pecora, A. L., & Goldberg, S. L. (2021). Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: a multi-center observational study. BMC Infectious Diseases, 21(1), 1-12.

Iwata-Yoshikawa, N., Okamura, T., Shimizu, Y., Hasegawa, H., Takeda, M., & Nagata, N. (2019). TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection. Journal of virology, 93(6), e01815-18.

Jia, H. P., Look, D. C., Shi, L., Hickey, M., Pewe, L., Netland, J., & McCray Jr, P. B. (2005). ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. Journal of virology, 79(23), 14614-14621.

Jie, Z., He, H., Xi, H., & Zhi, Z. (2020). Multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia. Expert Consensus on Chloroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia [in Chinese], 10, 1001-0939.

Keyaerts, E., Vijgen, L., Maes, P., Neyts, J., & Van Ranst, M. (2004). In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochemical and biophysical research communications, 323(1), 264-268.

Kim, T. S., Heinlein, C., Hackman, R. C., & Nelson, P. S. (2006). Phenotypic analysis of mice lacking the Tmprss2-encoded protease. Molecular and cellular biology, 26(3), 965-975.

Kupferschmidt, K., & Cohen, J. (2020). Race to find COVID-19 treatments accelerates.

Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., & Farzan, M. (2003). Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 426(6965), 450-454.

Liu, J., Cao, R., Xu, M., Wang, X., Zhang, H., Hu, H., ... & Wang, M. (2020). Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell discovery, 6(1), 1-4.

Lu, H. (2020). Drug treatment options for the 2019-new coronavirus (2019-nCoV). Bioscience trends, 14(1), 69-71.

Madrid, P. B., Panchal, R. G., Warren, T. K., Shurtleff, A. C., Endsley, A. N., Green, C. E., & Tanga, M. J. (2015). Evaluation of Ebola virus inhibitors for drug repurposing. ACS infectious diseases, 1(7), 317-326.

Marmor, M. F. (2020). COVID-19 and chloroquine/hydroxychloroquine: is there ophthalmological concern?. American journal of ophthalmology, 216, A1-A2.

Matsuyama, S., Nagata, N., Shirato, K., Kawase, M., Takeda, M., & Taguchi, F. (2010). Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. Journal of virology, 84(24), 12658-12664.

Menachery, V. D., Dinnon III, K. H., Yount Jr, B. L., McAnarney, E. T., Gralinski, L. E., Hale, A., & Baric, R. S. (2020). Trypsin treatment unlocks barrier for zoonotic bat coronavirus infection. Journal of virology, 94(5), e01774-19.

Millet, J. K., & Whittaker, G. R. (2014). Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein. Proceedings of the National Academy of Sciences, 111(42), 15214-15219.

Mitra, R. L., Greenstein, S. A., & Epstein, L. M. (2020). An algorithm for managing QT prolongation in coronavirus disease 2019 (COVID-19) patients treated with either chloroquine or hydroxychloroquine in conjunction with azithromycin: Possible benefits of intravenous lidocaine. HeartRhythm case reports, 6(5), 244.

Page, M.J., McKenzie, J.E., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., Shamseer, L., Tetzlaff, J.M., Akl, E.A., Brennan, S.E., et al. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. PLOS Medicine 18, e1003583.

Proano, C., & Kimball, G. P. (2019). Hydroxychloroquine retinal toxicity. New England Journal of Medicine, 380(17).

Retallack, H., Di Lullo, E., Arias, C., Knopp, K. A., Laurie, M. T., Sandoval-Espinosa, C., & DeRisi, J. L. (2016). Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proceedings of the National Academy of Sciences, 113(50), 14408-14413.

Riou, J., & Althaus, C. L. (2020). Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020. Eurosurveillance, 25(4), 2000058.

Rodriguez-Morales, A. J., Bonilla-Aldana, D. K., Balbin-Ramon, G. J., Rabaan, A. A., Sah, R., Paniz-Mondolfi, A., & Esposito, S. (2020). History is repeating itself: Probable zoonotic spillover as the cause of the 2019 novel Coronavirus Epidemic. Infez Med, 28(1), 3-5.

Schrezenmeier, E., & Dörner, T. (2020). Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nature Reviews Rheumatology, 16(3), 155-166.

Self, W. H., Semler, M. W., Leither, L. M., Casey, J. D., Angus, D. C., Brower, R. G., & Brown, S. M. (2020). Effect of hydroxychloroquine on clinical status at 14 days in hospitalized patients with COVID-19: a randomized clinical trial. JAMA, 324(21), 2165-2176.

Shulla, A., Heald-Sargent, T., Subramanya, G., Zhao, J., Perlman, S., & Gallagher, T. (2010). A transmembrane serine protease is linked to the SARS coronavirus receptor and activates virus entry. Journal of Virology.

Skipper, C. P., Pastick, K. A., Engen, N. W., Bangdiwala, A. S., Abassi, M., Lofgren, S. M., & Boulware, D. R. (2020). Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial. Annals of internal medicine, 173(8), 623-631.

Sogut, O., Can, M. M., Guven, R., Kaplan, O., Ergenc, H., Umit, T. B., ... & Cakmak, S. (2021). Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: a pilot observational study. The American journal of emergency medicine, 40, 41-46.

Van Den Brand, J. M. A., Haagmans, B. L., van Riel, D., Osterhaus, A. D. M. E., & Kuiken, T. (2014). The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models. Journal of comparative pathology, 151(1), 83-112.

Vincent, M. J., Bergeron, E., Benjannet, S., Erickson, B. R., Rollin, P. E., Ksiazek, T. G., & Nichol, S. T. (2005). Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virology journal, 2(1), 1-10.

Wang, M., Cao, R., Zhang, L., Yang, X., Liu, J., Xu, M., & Xiao, G. (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell research, 30(3), 269-271.

World Health Organization. World health statistics 2021. World Health Organization, 2021. https://www.who.int/emergencies/diseases/novel-coronavirus-2019 (accessed on 20 05 2021).

Xia, W., Shao, J., Guo, Y., Peng, X., Li, Z., & Hu, D. (2020). Clinical and CT features in pediatric patients with COVID‐19 infection: different points from adults. Pediatric pulmonology, 55(5), 1169-1174.

Yang, Y., Du, L., Liu, C., Wang, L., Ma, C., Tang, J., & Li, F. (2014). Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus. Proceedings of the National Academy of Sciences, 111(34), 12516-12521.

Yazdany, J., & Kim, A. H. (2020). Use of hydroxychloroquine and chloroquine during the COVID-19 pandemic: what every clinician should know.

Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., & Tan, W. (2020). A novel coronavirus from patients with pneumonia in China, 2019. New England journal of medicine.

Downloads

Published

05/07/2021

How to Cite

ARAÚJO, F. E. A. de; ROCHA, J. M. C. da .; MARQUES, L. E. R. de M. .; MACEDO, K. L. da S. .; MELO, P. K. M. .; DUARTE, G. M. .; PINHEIRO, F. I.; GUZEN, F. P. Pharmacological effects of hydroxychloroquine in patients with COVID-19: Systematic literature review. Research, Society and Development, [S. l.], v. 10, n. 8, p. e7310817193, 2021. DOI: 10.33448/rsd-v10i8.17193. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/17193. Acesso em: 22 nov. 2024.

Issue

Vol. 10 No. 8

Section

Health Sciences

License

Copyright (c) 2021 Francisco Emanoel Alves de Araújo; João Matheus Caé da Rocha; Lucas Emmanuel Rocha de Moura Marques; Kellyson Lopes da Silva Macedo; Paloma Katlheen Moura Melo; Gabriella Mendes Duarte; Francisco Irochima Pinheiro; Fausto Pierdoná Guzen

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.